Commentary: Marihuana as Medicine

BETWEEN 1840 and 1900, European and American medical journals published more than 100
articles on the therapeutic use of the drug known then as Cannabis indica (or Indian hemp) and
now as marihuana. It was recommended as an appetite stimulant, muscle relaxant, analgesic,
hypnotic, and anticonvulsant. As late as 1913 Sir William Osler
recommended it as the most satisfactory remedy for migraine.

Today the 5000-year medical history of cannabis has been almost forgotten. Its use declined in the
early 20th century because the potency of preparations was variable, responses to oral ingestion
were erratic, and alternatives became available -- injectable opiates and, later, synthetic drugs such
as aspirin and barbiturates. In the
United States, the final blow was struck by the Marihuana Tax Act of 1937. Designed to prevent
nonmedical use, this law made cannabis so difficult to obtain for medical purposes that it was
removed from the pharmacopeia. It is now confined to Schedule I under the Controlled
Substances Act as a drug that has a high potential for abuse,
lacks an accepted medical use, and is unsafe for use under medical supervision.

In 1972 the National Organization for the Reform of Marijuana Laws petitioned the Bureau of
Narcotics and Dangerous Drugs, later renamed the Drug Enforcement Administration (DEA), to
transfer marihuana to Schedule II so that it could be legally prescribed. As the proceedings
continued, other parties joined, including the Physicians
Association for AIDS [acquired immunodeficiency syndrome] Care. It was only in 1986, after
many years of legal maneuvering, that the DEA acceded to the demand for the public hearings
required by law. During the hearings, which lasted 2 years, many patients and physicians testified,
and thousands of pages of documentation were introduced.
In 1988 the DEA's own administrative law judge, Francis L. Young, declared that marihuana in its
natural form fulfilled the legal requirement of currently accepted medical use in treatment in the
United States. He added that it was "one of the safest therapeutically active substances known to
man." His order that the marihuana plant be
transferred to Schedule II was overruled, not by any medical authority, but by the DEA itself,
which issued a final rejection of all pleas for reclassification in Mach 1992.

Meanwhile, a few patients have been able to obtain marihuana legally for therapeutic purposes.
Since 1978, legislation permitting patients with certain disorders to use marihuana with a
physician's approval has been enacted in 36 states. Although federal regulations and procedures
made the laws difficult to implement, 10 states eventually
established formal marihuana research programs to seek Food and Drug Administration (FDA)
approval for Investigational New Drug (IND) applications. These programs were later
abandoned, mainly because the bureaucratic burden on physicians and patients became intolerable.

Growing demand also forced the FDA to Institute an Individual Treatment IND (commonly
referred to as a Compassionate IND) for the use of physicians whose patients needed marihuana
because no other drug would produce the same therapeutic effect. The application process was
made enormously complicated, and most physicians did not want to
become involved, especially since many believed there was some stigma attached to prescribing
cannabis. Between 1976 and 1988 the government reluctantly awarded about a half dozen
Compassionate INDs for the use of marihuana. In 1989 the FDA was deluged with new
applications from people with AIDS, and the number granted rose to 34 within a
year. In June 1991, the Public Health Service announced that the program would be suspended
because it undercut the administration's opposition to the use of illegal drugs. After that no new
Compassionate INDs were granted, and the program was discontinued in March 1992. Eight
patients are still receiving marihuana under the original
program; for everyone else it is officially a forbidden medicine.

And yet physicians and patients in increasing numbers continue to relearn through personal
experience the lessons of the 19th century. Many people know that marihuana is now being used
illegally for the nausea and vomiting induced by chemotherapy. Some know that it lowers
intraocular pressure in glaucoma. Patients have found it useful as
an anticonvulsant, as a muscle relaxant in spastic disorders, and as an appetite stimulant in the
wasting syndrome of human immunodeficiency virus infection. It is also being used to relieve
phantom limb pain, menstrual cramps, and other types of chronic pain, including (as Osler might
have predicted) migraine.2 Polls and voter referenda
have repeatedly indicated that the vast majority of Americans think marihuana should be medically
available.

One of marihuana's greatest advantages as a medicine is its remarkable safety. It has little effect
on major physiological functions. There is no known case of a lethal overdose; on the basis of
animal models, the ratio of lethal to effective dose is estimated as 40,000 to 1. By comparison, the
ratio is between 3 and 50 to 1 for
secobarbital and between 4 and 10 to 1 for ethanol. Marihuana is also far less addictive and far
less subject to abuse than many drugs now used as muscle relaxants, hypnotics, and analgesics.
The chief legitimate concern is the effect of smoking on the lungs. Cannabis smoke carries even
more tars and other particulate matter than tobacco
smoke. But the amount smoked is much less, especially in medical use, and once marihuana is an
openly recognized medicine, solutions may be found. Water pipes are a partial answer; ultimately
a technology for the inhalation of cannabinoid vapors could be developed. Even If smoking
continued, legal availability would make it easier to take
precautions against aspergilli and other pathogens. At present, the greatest danger in medical use
of marihuana is its illegality, which imposes much anxiety and expense on suffering people, forces
them to bargain with illicit drug dealers, and exposes them to the threat of criminal prosecution.

The main active substance in cannabis, [delta-9]- tetrahydrocannabinol ([delta-9]-THC), has been
available for limited purposes as a Schedule II synthetic drug since 1985. This medicine,
dronabinol (Marinol), taken orally in capsule form, is sometimes said to obviate the need for
medical marihuana. Patients and physicians who have tried
both disagree. The dosage and duration of action of marihuana are easier to control, and other
cannabinoids in the marihuana plant may modify the action of [delta-9]-THC. The development of
cannabinoids in pure form should certainly be encouraged, but the time and resources required are
great and at present unavailable. In these
circumstances, further isolation, testing, and development of individual cannabinoids should not
be considered a substitute for meeting the immediate needs of suffering people.

Although it is often objected that the medical usefulness of marihuana has not been demonstrated
by controlled studies, several informal experiments involving large numbers of subjects suggest an
advantage for marihuana over oral [delta-9]-THC and other medicines. For example, from 1978
through 1986 the state research program in New
Mexico provided marihuana or synthetic [delta-9]-THC to about 250 cancer patients receiving
chemotherapy after conventional medications failed to control their nausea and vomiting. A
physician who worked with the program testified at a DEA hearing that for these patients
marihuana was clearly superior to both chlorpromazine and synthetic
[delta-9]-THC.3 It is true that we do not have studies controlled according to the standards
required by the FDA -- chiefly because legal, bureaucratic, and financial obstacles are constantly
put in the way. The situation is ironical, since so much research has been done on marihuana,
often in unsuccessful attempts to prove its dangerous
and addictive character, that we know more about it than about most prescription drugs.

Physicians should offer more encouragement to controlled research, but it too has limitations.
Individual therapeutic responses can be obscured by the statistical results of group experiments in
which there is little effort to identify the specific features of a patient that affect the drug response.
Furthermore, much of our knowledge of
synthetic medicines as well as plant derivatives comes from anecdotal evidence. For example, as
early as 1976 several small, methodologically imperfect, and relatively obscure studies had shown
that taking an aspirin a day could prevent a second heart attack. In 1988 a large-scale experiment
demonstrated dramatic effects. This story is
suggestive, because marihuana, like aspirin, is a substance known to be unusually safe and to have
enormous potential health benefits.

Cannabis can also bring about immediate relief of suffering measurable in a study with only one
subject. In the experimental method known as the single patient randomized trial, active and
placebo treatments are administered randomly in alternation or succession to a patient. The
method is often useful when large scale controlled studies
are impossible or inappropriate because the disorder is rare, the patient is atypical, or the response
to the treatment is idiosyncratic. Many patients, either deliberately or because of unreliable
supplies, have informally carried out somewhat similar experiments by alternating periods of
cannabis use with periods of no use in the
treatment of various disorders.2(pp.133-135)

The American Medical Association was one of the few organizations that raised a voice in
opposition to the Marihuana Tax Act of 1937, yet today most physicians seem to take little active
interest in the subject, and their silence is often cited by those who are determined that marihuana
shall remain a forbidden medicine. Meanwhile, many
physicians pretend to ignore the fact that their patients with cancer, AIDS, or multiple sclerosis
are smoking marihuana for relief; some quietly encourage them. In a 1990 survey, 44% of
oncologists said they had suggested that a patient smoke marihuana for relief of the nausea
induced by chemotherapy.4 If marihuana were actually unsafe
for use even under medical supervision, as its Schedule I status explicitly affirms, this
recommendation would be unthinkable. It is time for physicians to acknowledge more openly that
the present classification is scientifically, legally, and morally wrong.

Physicians have both a right and a duty to be skeptical about therapeutic claims for any substance,
but only after putting aside fears and doubts connected with the stigma of illicit nonmedical drug
use. Advocates of medical use of marihuana are sometimes charged with using medicine as a
wedge to open a way for "recreational" use. The
accusation is false as applied to its target, but expresses in a distorted form a truth about some
opponents of medical marihuana; they will not admit that it can be a safe and effective medicine
largely because they are stubbornly committed to exaggerating its dangers when used for
nonmedical purposes.

We are not asking readers for immediate agreement with our affirmation that marihuana is
medically useful, but we hope they will do more to encourage open and legal exploration of its
potential. The ostensible indifference of physicians should no longer be used as a justification for
keeping this medicine in the shadows.